1. Field of the Invention
The present invention relates generally to an apparatus for and method of delivery of therapeutic substances. More specifically, the invention is directed to a medical assembly including a catheter having a transducer, which provides the driving force for transport of therapeutic substances into a tissue target area when an electrical signal with appropriate characteristics is applied to the transducer. A method of using the medical assembly is also described.
2. Description of the Related Art
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radically compress the atherosclerotic plaque of the lesion against the inner wall of the artery to dilate the arterial lumen. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient's vasculature.
In treating the damaged vascular tissue and to deter thrombosis and restenosis, therapeutic substances are commonly administered systemically. For example, anticoagulants, antiplatelets and cytostatic agents are commonly used to prevent thrombosis of the coronary lumen, to inhibit development of restenosis, and to reduce post-angioplasty proliferation of the vascular tissue, respectively.
Systemic administration of such therapeutic substances in sufficient amounts to supply an efficacious concentration to the local treatment site often produces adverse or toxic side effects for the patient. Accordingly, local delivery is a preferred method of treatment since smaller total levels of medication are administered in comparison to systemic dosages, but the medication is concentrated at a specific treatment site. Local delivery thus produces fewer side effects and achieves more effective results.
However, even with most local drug delivery devices used in conjunction with PTCA, a large majority of the drug does not go into the artery itself, but is flushed downstream and away from the target treatment area. Therefore, improvements in the efficiency of delivery of therapeutic substances into coronary arteries continue to be sought.
Phonophoresis, also referred to as sonophoresis, is a transport mechanism that uses ultrasonic or high frequency sound waves to drive an agent into the tissues of the passageway and, if desired, to increase cellular uptake. These sound waves may be produced by, for example, a transducer. Phonophoresis has several advantages over other drug delivery techniques, such as porous balloons and iontophoresis, including the ability to achieve greater penetration into the internal body tissue, and the capacity of not being limited to ionic charged forms of the agent. U.S. Pat. No. 5,800,392 to Racchini is an example illustrating the use of phonophoresis for the local delivery of a therapeutic substance or substances.
Phonophoresis is also advantageous because it increases tissue temperature, tissue permeability (i.e., permeability of the extracellular matrix), capillary permeability, and cellular permeability. These factors enhance intra-tissue transport of an agent, and cause vasodilation/relaxation, which may be beneficial in vascular applications of the present invention.
FIG. 1 illustrates a common commercial design of a phonophoresis device 2, which includes a transducer 4 mounted on a lumen 6 of a catheter 8. Transducer 4 may be disposed within a balloon 10. A disadvantage associated with this design includes the absorption of ultrasonic sound waves by lumen 6 upon which transducer 4 is mounted, thus reducing the total energy available for transporting therapeutic substances. To increase the effectiveness of the performance of the transducer, the intensity of the operating power of the transducer has to be increased. However, higher intensity operating power generates greater heat which can irreparably damage the tissues which are being treated. Accordingly, there is a constant tradeoff between increasing the performance of transducer 4 and maintaining the heat at a temperature at which tissues cannot be damaged. Additionally, transducer 4 is made from an inflexible ceramic material which significantly limits the ability of catheter 8 to flexibly navigate and maneuver through the vasculature of the subject.
What is needed is an improved transducer design which allows an operator to increase the intensity of the ultrasonic field generated by the transducer, thereby increasing the diffusion rate of therapeutic substances during phonophoresis, without excessively increasing the production of heat. Further desirable characteristics include, but are not limited to, increased efficiency of the phonophoresis process, and a transducer that can be more easily navigated through the tortuous vasculature of a subject.